title: Impaired natural killer cell function as a consequence of aging.
abstract: Alex Comfort wrote (1979): "... nobody needs long-lived mice." His point was, of course, that as much as possible, research should be done with humans "... who are the beneficiaries in mind ..." In this paper we hope to show that long-lived mice have been useful, if not essential, for conducting studies on the aging of innate immunity, specifically the NK cell component of the system. NK cells are activated early in the course of Trypanosoma musculi infections, which we employ as a model. We have generated evidence that the relatively severe infections of aged mice with T. musculi, are attributable, in part, to (a) functionally defective NK cells, the defect(s) being retained by LAK cells that arise from them, and (b) deficient amounts of IL-2 required to convert NK to LAK cells. Defective macrophages, which are the effector cells responsible for eliminating T. musculi, may also accumulate in aged animals. We postulate that the functionally deficient NK cells fail to generate adequate amounts of IFN gamma (and perhaps, TNF alpha) to optimally activate macrophages. This inadequacy can explain the weak ability of aged mice to control the early stage of T. musculi infection preceding the appearance of the more slowly-developing acquired immune response.
authors.affiliation: Department of Microbiology and Immunology, George Washington University School of Medicine, Washington, DC 20037, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Albright
authors.forename: J F
authors.initials: JF
authors.lastname: Albright
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D007107:Immune System / Q000502:physiology*; D007376:Interleukin-2 / Q000172:deficiency; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008809:Mice, Inbred C3H; D014352:Trypanosomiasis / Q000276:immunology*
chemical_list: D007376:Interleukin-2